Cellular Respiration: Glycolysis, Krebs Cycle, and Chemiosmosis

Posted on Dec 3, 2024 in Biology

Glycolysis

Glycolysis converts glucose into pyruvate through a sequence of 10 enzyme-catalyzed reactions. It consists of two main stages:

  1. Preparatory Stage: Glucose is phosphorylated, consuming two ATP molecules, and ultimately producing two molecules of glyceraldehyde-3-phosphate. The phosphorylation of glucose prevents it from leaving the cell.
  2. Second Stage: The two glyceraldehyde-3-phosphate molecules are oxidized by NAD+ and converted to pyruvate, generating four ATP molecules. The net energy yield of glycolysis is two ATP molecules per glucose molecule.

Reactions of Glycolysis:

  1. Glucose is phosphorylated by ATP to glucose-6-phosphate (irreversible).
  2. Glucose-6-phosphate is isomerized to fructose-6-phosphate.
  3. Fructose-6-phosphate is phosphorylated by ATP to fructose-1,6-bisphosphate.
  4. Fructose-1,6-bisphosphate is split into glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
  5. G3P continues in glycolysis. DHAP is readily converted to G3P. The outcome of this stage is two G3P molecules per glucose and a net consumption of two ATP.
  6. G3P is oxidized and phosphorylated, producing the first high-energy phosphate intermediate. This is a central reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase.
  7. 1,3-Bisphosphoglycerate (1,3-BPG) donates a phosphate to ADP, forming ATP and 3-phosphoglycerate.
  8. 3-Phosphoglycerate is converted to 2-phosphoglycerate.
  9. 2-Phosphoglycerate is dehydrated to phosphoenolpyruvate (PEP), the second high-energy phosphate intermediate.
  10. PEP transfers its phosphate to ADP, forming ATP and pyruvate. This reaction is catalyzed by pyruvate kinase.

Energy Performance:

Two ATP molecules are consumed, and four are synthesized, resulting in a net yield of two ATP and two NADH molecules.

Alcoholic Fermentation

Certain yeasts (e.g., Saccharomyces) perform alcoholic fermentation, converting glucose into ethanol and CO2. Pyruvate is decarboxylated to acetaldehyde by pyruvate decarboxylase. Acetaldehyde acts as the final electron acceptor, being reduced by NADH to ethanol via alcohol dehydrogenase.

Energy Balance: One NADH is consumed per pyruvate, so two NADH are consumed per glucose molecule.

Krebs Cycle (Citric Acid Cycle)

The Krebs cycle is the final oxidative pathway for glucose and most metabolic fuels. It oxidizes the acetyl group from acetyl-CoA to CO2 through eight catalyzed reactions:

  1. Acetyl-CoA condenses with oxaloacetate to form citrate.
  2. Citrate is isomerized to isocitrate.
  3. Isocitrate is oxidized to α-ketoglutarate, producing NADH and CO2.
  4. α-Ketoglutarate is oxidatively decarboxylated to succinyl-CoA, producing NADH and CO2.
  5. Succinyl-CoA is converted to succinate, generating GTP.
  6. Succinate is oxidized to fumarate, reducing FAD to FADH2.
  7. Fumarate is hydrated to malate.
  8. Malate is oxidized to oxaloacetate, producing NADH.

Energy Balance:

The cycle yields two ATP, six NADH, and two FADH2 per glucose molecule.

Complete oxidation of glucose to CO2 and H2O yields four ATP, 10 NADH, and two FADH2.

Chemiosmotic Hypothesis

Protons released during the ionization of hydrogen carried by NADH and FADH2 accumulate in the mitochondrial matrix. The electron transport chain actively pumps protons from the matrix to the intermembrane space, creating a proton gradient.

Mechanism of ATP Synthesis

ATP synthase has two active sites with different affinities for ADP and phosphate. Without energy input, one site holds ATP, and the other has high affinity for ADP and phosphate. Energy input causes a conformational change, expelling ATP from the first site. The second site then binds ADP and phosphate, forming ATP, which remains bound until the next energy-driven conformational change.